Monocyte-derived CXCL7 peptides in the marrow microenvironment.
Journal: 2006/May - Blood
ISSN: 0006-4971
Abstract:
The marrow microenvironment consists of several different interacting cell types, including hematopoietic-derived monocyte/macrophages and nonhematopoietic-derived stromal cells. Gene-expression profiles of stromal cells and monocytes cultured together differ from those of each population alone. Here, we report that CXCL7 gene expression, previously described as limited to the megakaryocyte lineage, is expressed by monocytes cocultured with stromal cells. CXCL7 gene expression was confirmed by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), and secretion of protein was detected by enzyme-linked immunosorbent assay (ELISA) and Western blot. At least 2 stromal-derived activities, one yet to be identified, were required for optimal expression of CXCL7 by monocytes. NAP-2, the shortest form of CXCL7 detected in the coculture media, was confirmed to decrease the size and number of CFU-Meg colonies. The propeptide LDGF, previously reported to be mitogenic for fibroblasts, was not secreted by stimulated monocytes. The recombinant form of LDGF produced in a prokaryotic expression system did not have biologic activity in our hands. The monocytic source of CXCL7 was also detected by immunohistochemistry in normal bone marrow biopsies, indicating an in vivo function. We conclude that stromal-stimulated monocytes can serve as an additional source for CXCL7 peptides in the microenvironment and may contribute to the local regulation of megakaryocytopoiesis.
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Blood 107(9): 3520-3526
PMID: 16391012

Monocyte-derived CXCL7 peptides in the marrow microenvironment

From the Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; and the Department of Medicine, University of Washington School of Medicine, Seattle, WA.
Reprints: Beverly Torok-Storb, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, D1-100, PO Box 19024, Seattle, WA 98109-1024; e-mail: gro.crchf@tskorotb.
Reprints: Beverly Torok-Storb, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, D1-100, PO Box 19024, Seattle, WA 98109-1024; e-mail: gro.crchf@tskorotb.
Received 2005 Oct 31; Accepted 2005 Dec 28.
Copyright © 2006, The American Society of Hematology

Abstract

The marrow microenvironment consists of several different interacting cell types, including hematopoietic-derived monocyte/macrophages and nonhematopoietic-derived stromal cells. Gene-expression profiles of stromal cells and monocytes cultured together differ from those of each population alone. Here, we report that CXCL7 gene expression, previously described as limited to the megakaryocyte lineage, is expressed by monocytes cocultured with stromal cells. CXCL7 gene expression was confirmed by quantitative reverse transcriptase–polymerase chain reaction (RT-PCR), and secretion of protein was detected by enzyme-linked immunosorbent assay (ELISA) and Western blot. At least 2 stromal-derived activities, one yet to be identified, were required for optimal expression of CXCL7 by monocytes. NAP-2, the shortest form of CXCL7 detected in the coculture media, was confirmed to decrease the size and number of CFU-Meg colonies. The propeptide LDGF, previously reported to be mitogenic for fibroblasts, was not secreted by stimulated monocytes. The re-combinant form of LDGF produced in a prokaryotic expression system did not have biologic activity in our hands. The monocytic source of CXCL7 was also detected by immunohistochemistry in normal bone marrow biopsies, indicating an in vivo function. We conclude that stromal-stimulated monocytes can serve as an additional source for CXCL7 peptides in the microenvironment and may contribute to the local regulation of megakaryocytopoiesis.

Abstract

Acknowledgments

We thank Dr Michael A. Harkey at the Center for Excellence in Molecular Hematology (CCEMH) at the FHCRC for help with cloning and recombinant protein expression; Dr Julie Randolph-Habecker at the Experimental Histopathology at the FHCRC for preparing and evaluating the immune histochemical sections; Ludmila Golubev, Gretchen Johnson, and Abigail Cruz for maintaining tissue culture; and Bonnie Larson and Helen Crawford for preparing the manuscript.

Acknowledgments

Notes

Prepublished online as Blood First Edition Paper, January 3, 2006; DOI 10.1182/blood-2005-10-4285.

Supported by the National Institutes of Health (grant T32CA09515) (M.M.P.), (grants R01HL62923 and P30DK56465) (B.T.-S.), and by the Ladies Auxiliary to the Veterans of Foreign Wars of the United States (M.M.P.).

M.M.P. designed and performed the experiments, analyzed the data, and wrote the manuscript; M.I. helped design and perform some of the experiments and analyze the data and edited the manuscript; N.A. performed the microarray analysis; L.G. performed the microarray analysis and edited the manuscript; B.T.-S. designed the experiments, provided critical oversight and research support, and edited the manuscript.

The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked “advertisement” in accordance with 18 U.S.C. section 1734.

Notes
Prepublished online as Blood First Edition Paper, January 3, 2006; DOI 10.1182/blood-2005-10-4285.
Supported by the National Institutes of Health (grant T32CA09515) (M.M.P.), (grants R01HL62923 and P30DK56465) (B.T.-S.), and by the Ladies Auxiliary to the Veterans of Foreign Wars of the United States (M.M.P.).
M.M.P. designed and performed the experiments, analyzed the data, and wrote the manuscript; M.I. helped design and perform some of the experiments and analyze the data and edited the manuscript; N.A. performed the microarray analysis; L.G. performed the microarray analysis and edited the manuscript; B.T.-S. designed the experiments, provided critical oversight and research support, and edited the manuscript.
The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked “advertisement” in accordance with 18 U.S.C. section 1734.

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